Trial of Ondansetron as a Parkinson's HAllucinations Treatment (TOP HAT)

TOPHAT (Trial of Ondansetron as a Parkinson's HAllucinations Treatment) is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial of ondansetron (8-24mg/day) as a treatment for Parkinson's hallucinations, with a 12-week primary outcome and follow-up to 24 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Dementia With Lewy Bodies; Parkinson's Hallucinations
• Intervention / Treatment: Drug: Ondansetron 8mg or matched placebo tablets

Detailed Description

This study investigates whether ondansetron, a drug used to treat post-operative sickness, has a meaningful treatment effect on Parkinson's hallucinations, and whether the drug is safe and cost effective for use in the NHS. We will compare ondansetron to placebo (a tablet that looks identical but contains no drug) over 12 weeks treatment, with follow up (once treatment ends) for a further 12 weeks. Assessments of symptoms will be carried out during treatment (after 6 and 12 weeks), and once treatment ends (18, 24 weeks), to measure hallucinations, delusions (false beliefs), Parkinson's symptoms (tremor, anxiety, sleep disturbance), memory, quality of life, possible side-effects such as constipation and headache, and the proportion of people who drop out due to side effects, or require additional treatment for their hallucinations. Blood drug concentration (measured after 6 and 12 weeks) will provide information on how quickly the drug is cleared from the body, and how this relates to treatment effects and side-effects, to guide future prescribing in people with Parkinson's. Based on knowledge of the average hallucinations scores in previous Parkinson's treatment studies, 306 people will be needed for the study to detect a meaningful treatment effect. The study will run for 4 years and involves a series of linked stages: (1) Trial set up across 20-30 UK centres; (2) Recruitment over 2 years; (3) Completion of follow up; and analysis, publication and dissemination of results.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Olga Zubko, PhD; Phone Number: 020 76759073; Email: o.zubko@ucl.ac.uk
• Study Contact Backup: Name: Suzanne Reeves; Email: suzanne.reeves@ucl.ac.uk

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom
    • Grampian
  • Bangor, United Kingdom
    • Betsi Cadwaladr
  • Bury, United Kingdom
    • Pennine
  • Cambridge, United Kingdom
    • Addenbrookes
  • Dartford, United Kingdom
    • Dartford
  • Dundee, United Kingdom
    • Tayside
  • Glasgow, United Kingdom
    • Glasgow
  • London, United Kingdom
    • Barking
  • London, United Kingdom
    • Bart's Health
  • London, United Kingdom
    • Imperial College NHS
  • London, United Kingdom
    • Lewisham
  • London, United Kingdom
    • Luton & Dunstable
  • London, United Kingdom
    • UCLH NHS foundation trust
  • Newcastle, United Kingdom
    • Newcstle
  • Newport, United Kingdom
    • Anuerin Bevan
  • North Shields, United Kingdom
    • Northumbria
  • Oxford, United Kingdom
    • Oxford
  • Peterborough, United Kingdom
    • North West Anglia
  • Poole, United Kingdom
    • Dorset
  • Redruth, United Kingdom
    • Cornwall
  • Salford, United Kingdom
    • Salford
  • Stoke, United Kingdom
    • North Midlands
  • Sutton In Ashfield, United Kingdom
    • Sherwood Forest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged over 18 years.
2. Meet MDS criteria for Parkinson's disease or revised criteria for DLB.
3. Score of 3 or more on the SAPS-H visual hallucinations item, indicating the presence of visual hallucinations at least weekly in the previous month.
4. Score of 3 or more on SAPS-H global rating, indicating moderate symptom severity.
5. Score of 4 or more on CGI-S, indicating moderate symptom severity.
6. On a stable dose of anti-Parkinson's medication, cholinesterase inhibitor or memantine for at least 28 days.
7. Capacity to give informed consent or, if lacking, legal representative able to give consent.

8. Pre-menopausal women, and men whose partners are of child bearing potential will agree to use effective contraception. 9) If treated with an antipsychotic drug at the time of enrolment, can still participate, provided the drug is stopped the day before trial medication is commenced.

   -

Exclusion Criteria:

1. Bradycardia (<50 bpm) (rescreen if reversible).
2. Congenital long QTc syndrome or presence of clinically significant prolongation of QTc (>460 ms for men or >470 ms for women) on ECG screening.
3. Severe hepatic failure (bilirubin >50 micromole/L)
4. Prescribed apomorphine (if apomorphine is discontinued, rescreen once stable on an alternative anti-Parkinson's treatment).
5. Prescribed tropisetron, granisetron, dolasetron.
6. History of hypersensitivity to ondansetron and its excipients (or those of placebo) or drugs listed in 5).

7. Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days.

   -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Treatment; Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron.	Drug: Ondansetron 8mg or matched placebo tablets; Participants will take one tablet daily in weeks 1 and 2, two tablets daily in weeks 3 and 4 and 3 tablets daily in weeks 5 and 6. Dose escalation will be guided by tolerability, through telephone safety monitoring prior to each dose increase; Other Names: Tablet, film coated
Placebo Comparator: Matched placebo; Participants randomised to the placebo treatment arm will take matched placebo, administered as tablets.	Drug: Ondansetron 8mg or matched placebo tablets; Participants will take one tablet daily in weeks 1 and 2, two tablets daily in weeks 3 and 4 and 3 tablets daily in weeks 5 and 6. Dose escalation will be guided by tolerability, through telephone safety monitoring prior to each dose increase; Other Names: Tablet, film coated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hallucinations	Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delusions	Scale for Assessment of Positive Symptoms-Delusions (0-65 points, higher scores indicate greater symptom severity	2, 4, 6, 12, 18, 24 weeks
Safety and tolerability	Number of Participants With Treatment-Related Adverse Events	2, 4, 6, 12, 18, 24 weeks
Health related quality of life	EQ-5D-5L	6, 12, 18, 24 weeks
Cost effectiveness	Health and social service utilisation	2, 4, 6, 12, 18, 24 weeks
Pharmacokinetics, plasma concentrations of the study drug	Measured using a validated HPLC/MS assay	6, 12 weeks
Hallucinations	Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations	2, 4, 6, 18, 24 weeks
Global illness severity	Clinical Global Impression of Severity Scale (1-7, higher scores indicate greater severity)	2, 4, 6, 12, 18, 24 weeks
Non-motor symptoms	Non-motor symptoms scale (0-120, higher scores indicate greater severity	2,4,6,12,18,24 weeks
Cognition	Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)	12 weeks
Hallucinations	University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)	6, 12 weeks
Feasibility and Acceptability of Video Consultation	The feasibility of video consultation will be measured at baseline, 6 and 12 weeks by the proportion of participants who were able to successfully attend on at least one occasion, the proportion who successfully attended all three assessments, and a Satisfaction questionnaire that allows both quantitative and qualitative information to be collected.	baseline, 6 and 12 weeks

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: MODEPHARMA Limited; PARKINSONS UK; PRIMENT; SEALED ENVELOPE; Wasdell Packaging Ltd; Custom Pharmaceuticals Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Perceptual Disorders; Parkinson Disease; Lewy Body Disease; Hallucinations; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Ondansetron
• Other Study ID Numbers: 17/0909

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No